Cyclic 3-deaza-adenosine diphosphoribose: a potent and stable analog of cyclic ADP-ribose.
Cyclic 3-deaza-adenosine diphosphoribose: a potent and stable analog of cyclic ADP-ribose.
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环状 3-脱氮腺苷二磷酸核糖：环状 ADP-核糖的有效且稳定的类似物。
DOI：
10.1016/s0304-4165(99)00161-0
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Walseth,TF
中科院分区：
文献类型：
--
作者：
Wong,L;Aarhus,R;Lee,HC;Walseth,TF
合成了环腺苷二磷酸核糖（cADPR）的类似物环3-脱氮腺苷二磷酸核糖（3-deaza-cADPR）。3-脱氮-cADPR与cADPR的不同之处仅在于嘌呤环3位的碳取代氮。与cADPR类似，该类似物在海胆卵匀浆中具有有效的钙释放活性，并且能够在低至0.3 nM的浓度下诱导钙释放。3-deaza-cADPR诱导的钙释放的EC 50值为1 nM，比cADPR强约70倍。3-deaza-cADPR诱导的钙释放特性在其他方面与cADPR相似。因此，3-deaza-cADPR和cADPR能够交叉脱敏，并且它们的钙释放活性被Sr 2+和咖啡因增强。cADPR的选择性拮抗剂8-amino-cADPR也能抑制3-deaza-cADPR诱导的钙释放。总之，这些数据表明3-脱氮-cADPR通过与cADPR相同的机制释放钙。发现3-脱氮-cADPR对热和酶水解都有抗性。煮沸2 h后，3-deaza-cADPR的破坏率仅为15%。当在cADPR完全水解的条件下用CD 38处理时，未观察到3-脱氮-cADPR的损失。因此，3-deaza-cADPR是cADPR的有效且稳定的类似物。这些特性使3-deaza-cADPR成为研究cADPR作用机制的有用探针。
Cyclic 3-deaza-adenosine diphosphoribose (3-deaza-cADPR), an analog of cyclic adenosine diphosphoribose (cADPR) was synthesized. 3-deaza-cADPR differs from cADPR by only the substitution of carbon for nitrogen at the 3-position of the purine ring. Similar to cADPR, the analog has potent calcium releasing activity in sea urchin egg homogenates and was able to induce calcium release at concentrations as low as 0.3 nM. The EC50value for 3-deaza-cADPR-induced calcium release was 1 nM, which is about 70 times more potent than cADPR. The properties of calcium release induced by 3-deaza-cADPR in all other respects were similar to those of cADPR. Thus, 3-deaza-cADPR and cADPR were capable of cross-desensitizing each other and their calcium releasing activities were potentiated by Sr2+as well as caffeine. 8-amino-cADPR, a selective antagonist of cADPR, was also able to inhibit 3-deaza-cADPR induced calcium release. Taken together, these data suggest that 3-deaza-cADPR releases calcium through the same mechanism as cADPR. 3-deaza-cADPR was found to be resistant to both heat and enzymatic hydrolysis. Only 15% of 3-deaza-cADPR was destroyed after boiling this compound for 2 h. No loss of 3-deaza-cADPR was observed when treated with CD38 under conditions where cADPR was completely hydrolyzed. Thus, 3-deaza-cADPR is a potent and stable analog of cADPR. These properties should make 3-deaza-cADPR a useful probe in studies focused on the mechanism of cADPR action.